Long term objective. The objective of the COBALT (Comorbid Affective Disorders, AIDS/HIV, and Long Term Health) study is to address an important gap in research evidence for cost-effective, scalable interventions for HIV positive adults on antiretroviral treatment (ART) with depression in low resource settings. Specific aims. COBALT has 4 aims: (1). To improve HIV outcomes and ART adherence through improved identification and management of depression, alcohol misuse and chronic diseases of lifestyle. (2). To improve comorbid depression outcomes in patients receiving ART through improved detection and management using a stepped care model. (3) To reduce the risk profile among ART patients for: (i) alcohol misuse disorders; and ii) cardiovascular disease and its risk factors through improved detection and management of these conditions. (4) To improve integrated treatment/care of long-term conditions at the primary health care level among patients receiving ART and to evaluate the health synergies and health systems implications, including cost-effectiveness of better integrated care. Research design and methods. We plan to conduct a cluster randomised controlled trial at the level of health clinics in the North West Province in South Africa. Compared with the 'usual treatment' control clinics, the experimental clinics will be enhanced using two interventions which we have previously successfully piloted, evaluated and implemented. (1) a guideline-based training programme for nurses that integrates the management of non-communicable and mental health conditions with infectious diseases, and whose predecessor has been adopted by the national government and implemented at scale reaching 18,000 health workers in 1,700 clinics throughout the country. (2) A group psychosocial intervention delivered by lay counselors, which has been successfully piloted in the KwaZulu-Natal Province. Task- shifting is central to these interventions, and necessary if we are to test an intervention capable of being scaled-up within settings so limited by the availabiliy of skilled human resources. We therefore propose the COBALT trial to evaluate the real-world effectiveness and cost-effectiveness of a facility-based intervention combining for people with HIV/AIDS: (i) case-detection and management of depression and chronic diseases of lifestyle, notably hypertension, diabetes, cardiovascular disease and alcohol misuse by nurses, with (ii) group psychosocial intervention for depression delivered by lay counselors, to improve both mental health and HIV outcomes in depressed adults receiving ART.